Hyperresponsiveness to adenosine in sensitized Wistar rats over-expressing A1 receptor
Hyperresponsiveness to adenosine in sensitized Wistar rats over-expressing A1 receptor
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DOI：
10.1016/j.ejphar.2012.09.002
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发表时间：
2012-11-15
影响因子：
5
通讯作者：
Cicala, Carla
中科院分区：
文献类型：
--
作者：
Alfieri, Alessio;Parisi, Antonio;Cicala, Carla
气道高反应性的特征是对支气管收缩刺激的反应性增加，这是哮喘的标志。腺苷是一种由 ATP 分解代谢产生的普遍存在的信号核苷，其细胞外水平在细胞损伤或应激后增加。腺苷在哮喘中发挥作用；哮喘患者（而非正常受试者）在吸入腺苷或其前体 5'-单磷酸腺苷后，最有可能通过肥大细胞上的腺苷 A(2B) 受体出现支气管收缩。然而，哮喘患者气道平滑肌对腺苷敏感性增加的机制仍有待阐明。早期实验研究表明 A(1) 受体参与其中；最近对豚鼠的研究证实了这一假设，并且哮喘支气管组织中腺苷 A(1) 表达增加的发现也证实了这一假设。挪威棕色大鼠（通常用于评估哮喘模型的品系）在过敏原激发后 3 小时（而非 24 小时）出现对腺苷的高反应性，且不涉及 A(1) 受体。在这里，我们研究了腺苷 A(1) 受体在致敏 Wistar 大鼠中的作用，该大鼠在过敏原攻击后 24 小时表现出气道高反应性。我们发现，在受到过敏原攻击的致敏 Wistar 大鼠的支气管上，平滑肌上的腺苷 A(1) 受体表达增加，这导致对腺苷和卵清蛋白的高反应性。 (C) 2012 Elsevier B.V. 保留所有权利。
Airway hyperreactivity is characterized by increased responsiveness to bronchoconstrictor stimuli and it is hallmark of asthma. Adenosine is an ubiquitous signaling nucleoside resulting from ATP catabolism, whose extracellular levels increase following cellular damage or stress. Adenosine plays a role in asthma; asthmatics, but not normal subjects, present bronchoconstriction following inhalation of adenosine or of its precursor, adenosine-5'-monophosphate, most likely via adenosine A(2B) receptor on mast cells. However, the mechanism underling the increased airway smooth muscle sensitivity to adenosine in asthmatics remains to be elucidated. Early experimental studies suggested the involvement of A(1) receptor; this hypothesis has been confirmed by more recent studies on guinea pigs and is corroborated by the finding of an increased adenosine A(1) expression on asthmatic bronchial tissues. Brown Norway rats, the strain usually used to assess asthma models, develop hyperresponsiveness to adenosine 3 h following allergen challenge, but not 24 h thereafter, without involvement of A(1) receptor. Here, we investigated the role of adenosine A(1) receptor in sensitized Wistar rats showing airway hyperresponsiveness 24 h following allergen challenge. We found that on bronchi of sensitized Wistar rats challenged with allergen there is an increased adenosine A(1) receptor expression on smooth muscle that is responsible for hyperresponsiveness to adenosine and ovalbumin. (C) 2012 Elsevier B.V. All rights reserved.